CN105287537A - Vinpocetine pharmaceutical composition and application of vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency - Google Patents
Vinpocetine pharmaceutical composition and application of vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency Download PDFInfo
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- CN105287537A CN105287537A CN201410221739.5A CN201410221739A CN105287537A CN 105287537 A CN105287537 A CN 105287537A CN 201410221739 A CN201410221739 A CN 201410221739A CN 105287537 A CN105287537 A CN 105287537A
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- suplatast tosilate
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Abstract
The invention relates to a vinpocetine pharmaceutical composition and application of the vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency, in particular to application to medicines for improving brain metabolism and microcirculation, enhancing cognitive function, relaxing bladder detrusor, relieving urinary urgency and urinary incontinence and the like. The vinpocetine pharmaceutical composition is a pharmaceutical preparation prepared by compositing vinpocetine, suplatast tosilate and pharmaceutically acceptable excipients.
Description
Technical field:
The present invention relates to Vinpocetine medicine composition and the application in control stress incontinence and urgent micturition are compeled thereof, belong to the technical field of medicine.
Background technology:
Stress incontinence and urgent micturition are compeled, and refer to that the unexpected increase of abdominal pressure causes urine independently not flow out, and are not to be pressed by detrusor contractions or the tension force pressure of wall of urinary bladder to urine causes.Be characterized in without the enuresis under normal condition, and when abdominal pressure increases suddenly, urine flow out automatically.As cough, laugh, sneeze, jump, when removing weight, urine is not independently from the phenomenon that urethral orifice spills.China has entered aging peak, stress incontinence and urgent micturition compel this colony elderly patients that puzzle, learn according to Epidemiological study, the female group that old people is especially old, no matter in rural area or city, the sickness rate that stress incontinence and urgent micturition are compeled is in rising trend, and the sickness rate that in worldwide, stress incontinence and urgent micturition are compeled is 100 ~ 1,20/,100,000 populations, can't take care of oneself to bring white elephant to relatives and society.Therefore, Study and Development goes out the medicine that novel, effective, that side effect is little stress incontinence and urgent micturition compel is current problem demanding prompt solution.
Vinpocetine is a kind of natural drug obtained from periwinkle, belongs to indoles alkaloid.For cerebral vasodilator, phosphodiesterase activity can be suppressed, increase the effect of the courier c-GMP of vascular smooth muscle relaxation, optionally increase cerebral blood flow, can also platelet aggregation be suppressed in addition, reduce human blood viscosity, strengthen erythrocyte deformabiliy, improve blood fluidity and microcirculation, promote cerebral tissue ingestion of glucose, increase brain oxygen consumption, improve the pharmacological actions such as brain metabolism; Because this medicine is mainly applicable to old group at present, its untoward reaction, also brings certain trouble to old group, such as sometimes may bring leukopenia, transaminase's rising to some patients, cerebral anoxia, once in a while also show alkali phosphatase raise, blood urea nitrogen rising etc.In modern pharmacology research process, the discovery that research worker is surprised, in this drug use process, with suplatast tosilate drug combination, can obviously eliminate above-mentioned untoward reaction, completely solve the use limitation of said medicine, simultaneously, also find in research that this drug regimen uses, can be relaxed detrusor of bladder, in stress incontinence and urgent micturition are compeled, there is good curative effect, this pharmaceutical composition can make relevant oral formulations, simultaneously also be applicable to vein or muscle is injected, completely solve the limitation being only applicable to intravenous drip, compel to bring Gospel at stress incontinence and urgent micturition for old group, alleviate country and household economy burden and stress, all there is considerable economic and social benefit.
Summary of the invention:
The object of the invention is to be used by drug regimen, the limitation that some untoward reaction in solution vinpocetine drug use process and this pharmaceutical preparation use.For associated patient provides a kind of use safety, easily medicine, this drug regimen uses the limitation solving medication in stress incontinence and urgent micturition are compeled clinically simultaneously.
In order to solve the above problems, the present invention adopts following technical scheme:
The present invention relates to a kind of pharmaceutical composition of a kind of pharmaceutical composition, is formed by active component vinpocetine, suplatast tosilate and pharmaceutically acceptable excipient composition.
According to parts by weight, in this pharmaceutical composition, active component contains the vinpocetine of 1 ~ 30 part and the suplatast tosilate of 30 ~ 1 parts.
Above-mentioned active component preferably contains the vinpocetine of 1 part and the suplatast tosilate of 20 parts according to parts by weight.
The active component of said medicine comprises its optical isomer, pharmaceutical salts and hydrate.
Meanwhile, above-mentioned pharmaceutical composition, solves the limitation that this clinical drug at present uses, and adopts conventional method can make any preparation medically allowed, comprises oral formulations or ejection preparation.
Above-mentioned pharmaceutical composition is in lax detrusor of bladder, the application alleviated in patient's medicines such as urgent micturition is compeled, urinary incontinence.
Above-mentioned drug combination preparation, preferred ejection preparation, its preparation method is: get vinpocetine 1g, suplatast tosilate 20g, sodium chloride, 1,2-PD; Sodium chloride is dissolved to 20% aqueous solution of propylene glycol 500ml, adds vinpocetine, suplatast tosilate, is stirred to entirely molten, is cooled to room temperature in 60 ~ 70 DEG C of water-baths, and the water for injection added is to 1000ml, and mixing is rear with 0.22 μm of membrane filtration; The fill of filtrate sub-bottle, sealing, sterilizing, to obtain final product.
The applicant has carried out vinpocetine and the research of suplatast tosilate compositions pharmacodynamic experiment, to set forth the beneficial effect of pharmaceutical composition provided by the invention further.
The curative effect of medicine of the present invention is proved by following pharmacodynamic experiment:
The research that one pharmaceutical composition is compeled at stress incontinence and urgent micturition
1.1 Animals Male rats, body weight (200 ± 30) g, consonance medical university of Chinese Academy of Medical Sciences animal center provides.
1.2 medicines and reagent ISDN (Pacific Ocean, Tianjin drugmaker) and positive control medicine nifedipine (Taiyuan, Shanxi Pharma Inc.) use 0.5% sodium carboxymethyl cellulose (CMC) to make solvent in use, make suspension; Acecoline (Ach, Beijing chemical reagents corporation); The active mensuration test kit of the tissue protein content of detrusor of bladder, NO and nitricoxide synthase (NOS) builds up Bioengineering Research Institute by Nanjing to be provided, and all the other reagent are domestic analytical pure.Kirschner (Krebs) nutritional solution.
1.3 instrument tonotransducers (Xin Hang mechanical & electronic equipment corporation, Ltd of JZ101 Gaobeidian City); Signal recorder (Medlab-u-4cs, Nanjing Mei Yi scientific & technical corporation); Glass Syrup-homogenizing instrument (DY89-1 type, Ningbo new sesame scientific instrument institute).
Rat is hit unconsciously by the preparation of 1.4 in vitro bladder detrusor bars, broken end blood-letting is lethal, under trigonum, bladder is cut in crosscut, residue bladder with partial is cut open along bladder veutro center, (1-2mm is wide to cut two toroidal helical flesh bars with parallel blade along muscle fiber trend, 8-10cm is long), being placed in by flesh bar after wiping out mucous layer fills in the perfusion flesh groove of 10ml37 DEG C of Krebs liquid, and sustainable supply 95% oxygen and 5% carbon dioxide gas mixture, every 15min changes a Krebs liquid, and flesh bar gives the preload incubation of 1.5g.Flesh bar one end connects tonotransducer, and by the contraction movement of signal recorder record flesh bar, start to add medicine after the spontaneous activity steadily of flesh bar, each experiment all adopts the bladder muscle bar of different Mus, repeats 8 ~ 10 times.
The mensuration of 1.5 smooth muscle of bladder bar shrink tensions, shrinkage amplitude and frequency adds KCI (4910-2mol/L) or Ach (10-4mlo/L), to produce about 80% of maximum average shrinkage tension force after bladder bar Spontaneous Contraction is stable.Shrink stable after, successive adds variable concentrations pharmaceutical composition (10-6mol/L) and different pharmaceutical proportioning carries out orthogonal experiment, the shrink tension of bladder muscle bar, shrinkage amplitude and frequency in the 1min that record pharmaceutical composition exists.
1.6 detrusor of bladder are organized the mensuration detrusor of NO and NOS activity to be organized in pharmaceutical composition (10-4mol/L) and Vehicle controls CMC solution to hatch 1h (37 DEG C, pass to 95% oxygen and 5% carbon dioxide gas mixture therebetween, every 15min changes a Krebs liquid), get 200mg tissue shred add 5mlKrebs liquid glass Syrup-homogenizing instrument grinding get 200ul homogenate, by the activity of kit measurement NO and NOS.
1.7 statistical procedures medicines on the impact of mean tension, average shrinkage amplitude and average contraction frequency to change percentage ratio to represent and as statistics index.Be worth in contrast with mean tension, average shrinkage amplitude and average contraction frequency before administration, the respective value after administration is effect value, change percentage ratio (%)=effect value/control value × 100%.Control value: the meansigma methods before dosing in 1min; Effect value: after contraction movement is stablized in 5min, the meansigma methods in 1min.Data all represent by mean ± standard deviation (x ± s), use SPSS13.0 program, first each group of data are carried out to the anova inspection of Repeated Measurement Data, when there being statistically-significant difference, each medicine group and matched group Dunnett check, and the comparison between medicine group adopts StudentNewmanKeuls inspection; ISDN is hatched group and is adopted Student-t to check with comparing of matched group.P < 0.05 has statistical significance for difference.
2 results
2.1ISDN shows the result that affects that ACH causes blockage effect, compared with contrasting with solvent CMC, and the middle dosage group of ISDN and high dose group (10
-5mOL/L and 10
-4mOL/L) detrusor of bladder flesh bar mean tension, average shrinkage amplitude and average frequency all can be made obviously to decline (P < 0.05)
2.2ISDN shows the result that affects that KCI causes blockage effect, compared with contrasting with solvent CMC, and the impact of pharmaceutical composition on detrusor of bladder flesh bar mean tension, shrinkage amplitude and frequency all not obvious (P > 0.05)
The affect detrusor of 2.3 different ratio pharmaceutical compositions on detrusor of bladder tissue incubation liquid NO and NOS content is organized in pharmaceutical composition (10
-4mol/L) in solution after incubation 1H, strict guidance of pressing test kit, the content recording the NO of the detrusor of bladder flesh bar tissue of hatching through pharmaceutical composition is (0.11 ± 0.03) umol/gprot, compared with NO content (0.08 ± 0.02) umol/gprot of solvent CMC matched group, obvious rising (P < 0.05, n=8); The activity of NOS is (0.214 ± 0.04) U/mgprot, compared with NOS activity value (0.179 ± 0.022) U/mgprot in solvent CMC matched group, obviously raises (P < 0.05, n=8).
3 discuss
This research display pharmaceutical composition can block the detrusor of bladder flesh bar caused by ACh and shrink, but the detrusor of bladder flesh bar caused by KCl can not be blocked shrink, show pharmaceutical composition blocks cellular extrinsic AGB stars, not that the flesh bar caused by voltage dependent channel influx across membrane is shunk, but by contraction that the outer m receptor maneuverability calcium channel influx across membrane of T suppression cell causes; The pharmaceutical composition of this different ratio suplatast tosilate of 30 ~ 1 parts (vinpocetine of 1 ~ 30 part and) has significant curative effect in lax detrusor of bladder, alleviate the urinary incontinence that detrusor involuntary contraction causes, the clinical patient that can be used for treating stress incontinence and urgent micturition and compel.
Two pharmaceutical compositions are on leukocytic impact
4.1 materials and methods
4.1.1 material
4.1.1.1 drug pharmaceutical compositions.Compound method: take nicotiamide 7.3mg, adds RPMI-1640 culture fluid 3.65ml, is made into 2 × 10
3ug/ml medicinal liquid, then use culture fluid two-fold dilution, make final concentration be 1 × 10
3, 5 × 10
2, 2.5 × 10
2, 1.25 × 10
2ug/ml.
4.1.1.2 cell human peripheral leucocytes takes from blood station, center, Nanjing whole blood (AB type), is separated is prepared into 8 × 107/ml suspension with ficoll.
4.1.1.3 culture fluid and additament RPMI-1640 culture medium are purchased from Gibco company, new-born calf serum (superfine) is provided by Hangzhou four seasons Bioengineering Research Institute, and ficoll (29.8 ten thousand), K release (fMLP) are purchased from Sigma company.
4.1.2 experimental technique
4.1.2.1 step is poly-with 0.8% agarose-RPMI1640 culture medium mixed liquor bed board, solidification, punch three row, often row 6 hole, add respectively in setting hole containing variable concentrations and the proportioning suplatast tosilate of 30 ~ 1 parts (vinpocetine of 1 ~ 30 part and) pharmaceutical composition WBC suspension and carry out orthogonal experiment containing the RPMI1640 culture fluid (fMLP final concentration 10nmol/L) of fMLP, establish without medicine contrast, blank in experiment, 37 DEG C, cultivate 5h under 5%CO2,4 DEG C of dryings, fixing, dyeing.The parallel repetition of above-mentioned experiment 6 samples.
4.1.2.2 measure WBC displacement with mircrometer gauge under result viewing microscope, obtain chemotactic percentage rate with administration group and the ratio without the actual chemotactic distance average of medicine matched group.
4.1.2.3 statistical procedures linear regression equation asks IC50 value.
4.1.3 result
The pharmaceutical composition of experimental result display different ratio affects human leukocyte chemotactic, not obvious, the use of pharmaceutical composition, avoid the side effect that vinpocetine drug use causes human leukocytes to reduce, simultaneously, inventor is found by mouse experiment research, carries out the observation of transaminase's change, do not find the sign that transaminase raises at this pharmaceutical composition of long-term taking.The combinationally using as clinical application provides conveniently of this medicine for this reason.
Five detailed description of the invention
The preparation of embodiment 1 injection
1, prescription:
2, prepare:
Get vinpocetine, suplatast tosilate, sodium chloride, 1,2-PD; Sodium chloride is dissolved to 20% aqueous solution of propylene glycol 500ml, adds vinpocetine, suplatast tosilate, is stirred to entirely molten, is cooled to room temperature in 60 ~ 70 DEG C of water-baths, adds the water for injection of surplus to 1000ml, with 0.22 μm of membrane filtration after mixing.The fill of filtrate sub-bottle, sealing, sterilizing, to obtain final product.
The preparation of embodiment 2 drop pill
1, prescription:
2, prepare:
Taking polyethylene glycol 6000, is placed in container, is heated to 70-80 DEG C, treats whole melting, when temperature drops to about 50 DEG C, add vinpocetine, suplatast tosilate makes melting, temperature controls at 40-50 DEG C, pours dripping in pill dripping machine into, in instillation dimethicone, make drop pill, to obtain final product.
The preparation of embodiment 3 sublingual lozenge
1, prescription:
2, get vinpocetine, suplatast tosilate, hydroxypropyl emthylcellulose (E-50), hydroxypropyl emthylcellulose (E-4M), hydroxypropyl cellulose, micropowder silica gel, magnesium stearate to progressively increase method mix homogeneously with equivalent, be directly compressed into sublingual lozenge, obtain final product.
The preparation of embodiment 4 soft capsule
1, prescription:
2, prepare:
Getting gelatin adds in retort, under stirring, add suitable quantity of water, airtight, after gelatin dissolves completely, then adds glycerol, stirs, and vacuumize degassing 2 hours, puts into heat-preserving container, insulation hold over night, stand-by.Get soybean oil, lecithin, Cera Flava mix homogeneously, take vinpocetine, suplatast tosilate adds, stir, colloid mill is ground to colloidal, and room temperature leaves standstill.Medicinal liquid is poured in encapsulating machine, compacting soft capsule, dry, to obtain final product.
The preparation of embodiment 5 lyophilized formulations
1, prescription:
2, prepare:
Get vinpocetine, suplatast tosilate add ethanol in proper amount dissolve, add water for injection to 3000ml, pH value to 6.0 ~ 8.0 are regulated with sodium carbonate liquor, add mannitol, lactose makes to dissolve completely, carry out autoclave sterilization sterilizing by the requirement of injection, adopt filtering with microporous membrane, filtrate carries out subpackage by every 3ml, lyophilization, sealing, to obtain final product.
Claims (7)
1. a Vinpocetine medicine composition, is characterized in that described pharmaceutical composition is formed by active component vinpocetine, suplatast tosilate and pharmaceutically acceptable excipient composition.
2. pharmaceutical composition according to claim 1, is characterized in that active component is according to parts by weight: the suplatast tosilate containing the vinpocetine of 1 ~ 30 part and 30 ~ 1 parts.
3. pharmaceutical composition according to claim 2, is characterized in that active component is according to parts by weight: the suplatast tosilate containing the vinpocetine of 1 part and 20 parts.
4. pharmaceutical composition according to claims 1 to 3, is characterized in that described active component comprises optical isomer, pharmaceutical salts and hydrate.
5. pharmaceutical composition according to claim 1, is characterized in that this pharmaceutical composition can make the preparation medically allowed, comprises oral formulations or ejection preparation.
6. the pharmaceutical composition according to right 1, is characterized in that the application of this pharmaceutical composition in control stress incontinence and urgent micturition are compeled.
7. ejection preparation according to claim 5, gets vinpocetine 1g, suplatast tosilate 20g, sodium chloride, 1,2-PD; Sodium chloride is dissolved to 20% aqueous solution of propylene glycol 500ml, adds vinpocetine, suplatast tosilate, is stirred to entirely molten, is cooled to room temperature in 60 ~ 70 DEG C of water-baths, and the water for injection added is to 1000ml, and mixing is rear with 0.22 μm of membrane filtration; The fill of filtrate sub-bottle, sealing, sterilizing, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410221739.5A CN105287537A (en) | 2014-05-26 | 2014-05-26 | Vinpocetine pharmaceutical composition and application of vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency |
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|---|---|---|---|
| CN201410221739.5A CN105287537A (en) | 2014-05-26 | 2014-05-26 | Vinpocetine pharmaceutical composition and application of vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency |
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| CN105287537A true CN105287537A (en) | 2016-02-03 |
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| CN201410221739.5A Pending CN105287537A (en) | 2014-05-26 | 2014-05-26 | Vinpocetine pharmaceutical composition and application of vinpocetine pharmaceutical composition to prevention and treatment of stress urinary incontinence and urinary urgency |
Country Status (1)
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1205634A (en) * | 1995-08-08 | 1999-01-20 | 沃尔夫－乔治·霍斯曼 | Use of PDE inhibitors in manufacture of medicament for treatment of bladder diseases |
-
2014
- 2014-05-26 CN CN201410221739.5A patent/CN105287537A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1205634A (en) * | 1995-08-08 | 1999-01-20 | 沃尔夫－乔治·霍斯曼 | Use of PDE inhibitors in manufacture of medicament for treatment of bladder diseases |
Non-Patent Citations (3)
| Title |
|---|
| MICHAEL C. TRUSS ET AL.: "Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder", 《WORLD J UROL》 * |
| TOMOHIRO UEDA ET AL.: "Improvement of Interstital Cystitis Symptoms and Problems that Developed During Treatment with Oral IPD-1151T", 《THE JOURNAL OF UROLOGY》 * |
| 刘茂柏等主编: "《安全用药指导手册》", 31 August 2013, 厦门大学出版社 * |
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Application publication date: 20160203 |
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